Biosensor

ABSTRACT

An electrode layer comprising a working electrode  1  and a counter electrode  2,  and a reagent layer  10  are formed on an insulating support  5  and, further, a spacer  7  having a long and narrow cut-out portion on the reagent layer  10  is bonded to a cover  6  having an air hole  9  to form a cavity  12  that sucks blood as a liquid sample by capillary phenomenon, and a portion of side walls of the spacer  7  and the cover  6,  which side walls face the cavity  12,  is subjected to a treatment for making the portion itself have hydrophilicity.  
     In the biosensor constructed as described above, when blood is sucked from the cavity  12  by capillary phenomenon, the suction is promoted, and the performance of the sensor is improved. Further, the process of manufacturing the sensor is simplified, resulting in increased productivity.

TECHNICAL FIELD

[0001] The present invention relates to a biosensor for analyzing aspecific component in a liquid sample and, more particularly, to abiosensor having a cavity into which a liquid sample is drawn bycapillary phenomenon.

BACKGROUND ART

[0002] As a biosensor for analyzing a specific component in a liquidsample, there is, for example, a biosensor for detecting a blood sugarlevel or the like by measuring a current value obtained by a reactionbetween glucose in blood and a reagent such as glucose oxidase or thelike which is held in the sensor.

[0003]FIG. 4 is an exploded perspective view illustrating a conventionalbiosensor for measuring a blood sugar level as described above.

[0004] In FIG. 4, a working electrode 1 and a counter electrode 2 areformed by printing on an insulating support 5 comprising polyethyleneterephthalate or the like, and a reagent layer 10 including glucoseoxidase and an electron acceptor is formed on these electrodes and,further, a surfactant layer 11 comprising yolk lecithin or the like isformed on the reagent layer 10.

[0005] Furthermore, on the surfactant layer 11, a spacer 7 having a longand narrow cut-out portion on the electrodes and the reagent layer 10,and a cover 6 having an air hole are bonded together onto the insulatingsupport 5, to form a cavity 12 in which a specific amount of bloodsampled is made to react with the reagent layer 10, and a current valuegenerated by the reaction is detected with the electrodes.

[0006] In the biosensor constructed as described above, blood is drawnfrom a suction inlet 8 into the cavity 12 by capillary phenomenon, andguided to the position where the electrodes and the reagent layer 10 arepresent. Then, a current value generated by a reaction between the bloodand the reagent on the electrodes is read by an external measuringapparatus (not shown) that is connected to the biosensor through leads 3and 4, and a blood sugar level in the blood is obtained according to thecurrent value.

[0007] Conventionally, when blood is applied onto the suction inlet 8and sampled, in order to draw the blood quickly and deep into the cavity12 by capillary phenomenon, there has been devised that the surfactantlayer 11 is spread so as to cover the reagent layer 10.

[0008] However, in the conventional biosensor which facilitates drawingof blood into the cavity 12 by providing the surfactant layer 11 overthe reagent layer 10, since the blood is drawn into the cavity whiledissolving the surfactant layer 11 and, further, the blood reacts withthe reagent layer 10 on the electrodes while dissolving the reagentlayer 10, the surfactant layer 11 prevents the reagent layer 10 fromdissolving into the blood, and this causes variations in the sensitivityof the sensor or in the measured value, resulting in a detrimentaleffect on the performance of the sensor.

[0009] Further, in the construction of the conventional biosensor, afterthe reagent layer 10 is formed by spreading a solution including areagent and an electron acceptor over the electrodes and then drying thesolution, formation of the surfactant layer 11 on the reagent layer 10requires a step of applying and spreading a solution including asurfactant so as to cover the reagent layer 10, and a step of drying thesurfactant layer. Therefore, the process of manufacturing the biosensortakes much time, resulting in poor productivity.

[0010] The present invention is made to solve the above-describedproblems and has for its object to provide a biosensor that can promotethe flow of blood into the cavity to quickly and sufficiently draw theblood into the cavity, without forming a surfactant layer on the reagentlayer.

DISCLOSURE OF THE INVENTION

[0011] According to claim 1 of the present invention, in a biosensorwhich is provided with a cavity into which a liquid sample is drawn bycapillary phenomenon and is able to analyze a component in the liquidsample by a reaction between the drawn liquid sample and a reagent, thesurface itself of at least a portion of side walls of the sensor, saidside walls facing the cavity, has hydrophilicity.

[0012] According to the biosensor constructed as described above, sinceat least a portion of the side walls of the sensor, which side wallsface the cavity into which the liquid sample is drawn by capillaryphenomenon, has hydrophilicity at its surface, suction of the liquidsample can be promoted without providing a surfactant layer on thereagent that reacts with the liquid sample. Accordingly, the process ofmanufacturing the sensor can be simplified.

[0013] According to claim 2 of the present invention, in the biosensordefined in claim 1, the side walls of the sensor facing the cavity aremade of a resin material in which a surfactant is mixed.

[0014] According to the biosensor constructed as described above, sincethe side walls having hydrophilicity are made of a resin material inwhich a surfactant is mixed, suction of the liquid sample can bepromoted without providing a surfactant layer on the reagent that reactswith the liquid sample, and the process of manufacturing the sensor canbe simplified.

[0015] According to claim 3 of the present invention, in the biosensordefined in claim 2, the amount of the surfactant to be mixed is 0.01weight % or more.

[0016] According to the biosensor constructed as described above, sincethe side walls of the sensor facing the cavity are made of a resinmaterial into which a surfactant of 0.01 weight % or more is mixed,sufficient blood suction promoting effect can be achieved.

[0017] According to claim 4 of the present invention, in the biosensordefined in claim 1, the side walls of the sensor facing the cavity aremade of a film the surface of which is covered with a surfactant.

[0018] According to the biosensor constructed as described above, sincethe side walls of the sensor having hydrophilicity are made of a filmthe surface of which is covered with a surfactant, suction of the liquidsample can be promoted without providing a surfactant layer on thereagent that reacts with the liquid sample and, accordingly, the processof manufacturing the sensor can be simplified.

[0019] According to claim 5 of the present invention, in the biosensordefined in claim 1, the side walls of the sensor facing the cavity aremade of a film the surface of which is covered with a resin having ahydrophilic polar group.

[0020] According to the biosensor constructed as described above, sincethe side walls of the sensor having hydrophilicity are made of a filmthe surface of which is covered with a resin having a hydrophilic polargroup, suction of the liquid sample can be promoted without providing asurfactant layer on the reagent that reacts with the liquid sample and,accordingly, the process of manufacturing the sensor can be simplified.

[0021] According to claim 6 of the present invention, in the biosensordefined in claim 4 or 5, the thickness of the surfactant or the resinhaving a hydrophilic polar group, which covers the film, is several tensof angstroms or more.

[0022] According to the biosensor constructed as described above, sincethe side walls of the sensor facing the cavity are made of a film thatis covered with the surfactant or the resin having a hydrophilic polargroup, sufficient blood suction promoting effect can be achieved.

[0023] According to claim 7 of the present invention, in the biosensordefined in claim 1, the surface of at least a portion of the side wallsforming the cavity is chemically reformed.

[0024] According to the biosensor constructed as described above, sincethe surface of at least a portion of the side walls forming the cavityis chemically reformed to form the side walls of the sensor havinghydrophilicity, suction of the liquid sample can be promoted withoutproviding a surfactant layer on the reagent that reacts with the liquidsample, and accordingly, the process of manufacturing the sensor can besimplified.

[0025] According to claim 8 of the present invention, in the biosensordefined in claim 7, a hydrophilic functional group is formed on thesurface of at least a portion of the side walls facing the cavity, bysubjecting the surface to any of the following treatments: plasmadischarge, coupling reaction, ozone treatment, and UV treatment.

[0026] According to the biosensor constructed as described above, thesurface of at least a portion of the side walls forming the cavity issubjected to any of the following chemical surface treatments: plasmadischarge, coupling reaction, ozone treatment, and UV treatment, therebyforming a hydrophilic functional group on the surface. Therefore, thesurface of at least a portion of the side walls facing the cavity canhave hydrophilicity.

[0027] According to claim 9 of the present invention, in the biosensordefined in claim 1, the surface of at least a portion of the side wallsfacing the cavity is made of a rough surface.

[0028] According to the biosensor constructed as described above, sincethe surface of at least a portion of the side walls forming the cavityis roughened to form the side walls of the sensor having hydrophilicity,suction of the liquid sample can be promoted without providing asurfactant layer on the reagent that reacts with the liquid sample, andaccordingly, the process of manufacturing the sensor can be simplified.

[0029] According to claim 10 of the present invention, in the biosensordefined in claim 9, a rough surface is formed at the surface of at leasta portion of the side walls facing the cavity, by subjecting the surfaceto any of the following treatments: sand blasting, electric discharge,non-glare treatment, mat treatment, and chemical plating.

[0030] According to the biosensor constructed as described above, thesurface of at least a portion of the side walls forming the cavity issubjected to any of the following treatments: sand blasting, electricdischarge, non-glare treatment, mat treatment, and chemical plating,thereby forming a rough surface. Therefore, the surface of at least aportion of the side walls facing the cavity can have hydrophilicity.

[0031] According to claim 11 of the present invention, in the biosensordefined in any of claims 1 to 10, the surface of the support, on whichthe reagent that reacts with the liquid sample is formed, also hashydrophilicity.

[0032] According to the biosensor constructed as described above, notonly the surface of at least a portion of the side walls forming thecavity but also the surface of the support on which the reagent thatreacts with the liquid sample is formed, have hydrophilicity. Therefore,the area of the portion having hydrophilicity in the side walls facingthe cavity is increased, whereby the liquid sample can be drawn withhigher efficiency.

[0033] According to claim 12 of the present invention, in the biosensordefined in any of claims 1 to 10, the surface of the support, on whichelectrodes that detect the reaction between the liquid sample and thereagent are formed, also has hydrophilicity.

[0034] According to the biosensor constructed as described above, notonly the surface of at least a portion of the side walls forming thecavity but also the surface of the support on which the electrodes fordetecting the reaction between the liquid sample and the reagent areformed, have hydrophilicity. Therefore, the adhesion of the electrodesto the support on which the electrodes are formed is improved, and theproblem of electrode peeling is solved, whereby the reliability of thesensor is improved.

[0035] According to claim 13 of the present invention, in the biosensordefined in claim 12, the surface of the support is made of a roughsurface, and the level of the rough surface to be formed is 0.001 μm to1 μm.

[0036] According to the biosensor constructed as described above, sincea rough surface having unevenness in a level from 0.001 μm to 1 μm isformed at the surface of at least a portion of the side walls of thesensor facing the cavity, the adhesion is improved.

BRIEF DESCRIPTION OF THE DRAWINGS

[0037]FIG. 1 is an exploded perspective view illustrating a biosensorfor measuring a blood sugar level, according to embodiments of thepresent invention.

[0038]FIG. 2 is a graph showing the result of a comparison of thesensitivities to blood between a sensor according to Example 1 of theinvention and a conventional sensor.

[0039]FIG. 3 is a graph showing the result of a comparison of thesensitivities to blood between a sensor according to Example 2 of thepresent invention and a conventional sensor.

[0040]FIG. 4 is an exploded perspective view illustrating a conventionalbiosensor for measuring a blood sugar level.

BEST MODE TO EXECUTE THE INVENTION

[0041] Embodiment 1.

[0042] Hereinafter, a first embodiment of the present invention will bedescribed with reference to FIG. 1.

[0043] Initially, the construction of a biosensor according to the firstembodiment will be described with reference to FIG. 1.

[0044]FIG. 1 is an exploded perspective view of a biosensor according tothe first embodiment of the present invention, and this biosensor isdifferent from the conventional one in that the surfactant layer 11formed on the reaction reagent layer 10 is dispensed with and, as asubstitute for the surfactant layer 11, at least a portion of the sidewalls facing the cavity 12 into which blood is drawn, i.e., at least aportion of parts of the spacer 7 and the cover 6, which parts face thecavity 12, is made to have hydrophilicity by itself, to promote drawingof the blood.

[0045] Hereinafter, a description will be given of specific methods formaking the surfaces of the cover 6 and the spacer 7 facing the cavity 12have hydrophilicity.

[0046] One of the methods is as follows. An insulating film is formed bymixing a chemical having surface activity such as a surfactant or thelike into a material such as polyethylene terephthalate, polycarbonateor the like, and the cover 6 and the spacer 7 are constituted by theinsulating film. Thereby, the wettability of the side walls of thecavity 12 is increased, and the blood sampled from the suction inlet 8can be quickly and reliably drawn into the cavity 12.

[0047] The kinds of surfactants which can be expected to have theabove-mentioned effects when being mixed into the insulating film(classified as hydrophilic groups) are as follows: anionic surfactantssuch as carboxylate, sulfonate, carboxylate, ester phosphate, and thelike; cationic surfactants such as primary amine salt, secondary aminesalt, tertiary amine salt, quaternary ammonium salt, and the like;ampholytic surfactants such as amino-acid base surfactants, betaine basesurfactants, and the like; and non-ionic surfactants such aspolyethylene glycol base surfactants, polyalcohol base surfactants, andthe like.

[0048] Further, as materials of the cover 6 and the spacer 7 into whichthe above-mentioned surfactants can be mixed, there are, besides thosementioned above, polybutylene terephthalate, polyamide, polyvinylchloride, polyvinylidene chloride, polyimide, nylon, and the like.

[0049] As described above, according to the first embodiment of thepresent invention, the side walls facing the cavity 12 into which bloodis drawn, i.e., the portions of the cover 6 and the spacer 7 facing thecavity 12, are made to have hydrophilicity by mixing a chemical havingsurface activity such as a surfactant or the like into the materialitself of the cover 6 and the spacer 7. Therefore, the wettability ofthe side walls of the cavity 12 is increased, whereby the blood sampledfrom the suction inlet 8 can be quickly and reliably drawn into thecavity 12. Accordingly, the surfactant layer 11 on the reagent layer 10can be dispensed with, and the process of manufacturing the biosensorcan be simplified.

[0050] The blood suction promoting effect obtained by mixing thesurfactant into the insulating base material to be the cover 6 and thespacer 7 is sufficiently recognized when the surfactant of 0.01 weight %or more is added.

[0051] Embodiment 2.

[0052] Hereinafter, a second embodiment of the present invention will bedescribed with reference to FIG. 1.

[0053] Initially, the construction of a biosensor according to thesecond embodiment will be described with reference to FIG. 1. In thefirst embodiment, a surfactant is mixed into the material itself of thecover 6 and the spacer 7 to make the portions of the cover 6 and thespacer 7 facing the cavity 12 have hydrophilicity. On the other hand, inthis second embodiment, any of the surfactants described for the firstembodiment is applied onto an insulating film comprising polyethyleneterephthalate, polycarbonate, or the like and to be a base material ofthe cover 6 and the spacer 7, or a resin having a hydrophilic polargroup at its surface is laminated on the insulating film, so as to coatthe insulating film with the surfactant or the resin, thereby making theportions of the cover 6 and the spacer 7 facing the cavity 12 havehydrophilicity.

[0054] As the resin having a hydrophilic polar group, there are acrylicresin, polyester resin, urethan resin, and the like.

[0055] Further, when forming the hydrophilic coating on the surface ofthe insulating base material to be the cover 6 and the spacer 7, thebase material is not restricted to the above-mentioned insulating filmcomprising polyethylene terephthalate or polycarbonate, but othermaterials such as polybutylene terephthalate, polyamide, polyvinylchloride, polyvinylidene chloride, polyimide, and nylon may be employed.

[0056] Furthermore, hydrophilicity of the side walls of the cavity 12can be increased to enhance wettability of the side walls by subjectingthe surface of the insulating film comprising polyethyleneterephthalate, polycarbonate, or the like and to be the base material ofthe cover 6 and the spacer 7, to primer treatment using organotitaniumcompound, polyethylene imine compound, isocyanate compound, or the like.

[0057] As described above, according to the second embodiment, asurfactant is applied onto the insulating film to be the base materialof the cover 6 and the spacer 7, or a resin having a hydrophilic polargroup at its surface is laminated on the insulating film so as to coatthe surfaces of the cover 6 and the spacer 7 with the surfactant or theresin, whereby the side walls facing the cavity 12 into which blood isdrawn, i.e., the portions of the cover 6 and the spacer 7 facing thecavity 12, have hydrophilicity. Therefore, wettability of the side wallsof the cavity 12 is increased, whereby the blood sampled from thesuction inlet 8 can be quickly and reliably drawn into the cavity 12.Accordingly, the surfactant layer 11 on the reagent layer 10 isdispensed with, whereby the process of manufacturing the biosensor canbe simplified.

[0058] The blood suction promoting effect is recognized when thethickness of the surfactant layer applied onto the insulating film asthe base material of the cover 6 and the spacer 7 or the thickness ofthe resin layer having a hydrophilic polar radial to be laminated isseveral tens of angstroms or more. However, in order to sustain theabove-mentioned effect for long hours, the thickness is desired to beseveral hundreds of angstroms or more.

[0059] Embodiment 3.

[0060] Hereinafter, a third embodiment of the present invention will bedescribed with reference to FIG. 1.

[0061] Initially, the construction of a biosensor according to the thirdembodiment will be described with reference to FIG. 1. In the firstembodiment, a surfactant is mixed into the material itself of the cover6 and the spacer 7 to make the portions of the cover 6 and the spacer 7facing the cavity 12 have hydrophilicity. On the other hand, in thisthird embodiment, the surfaces of the cover 6 and the spacer 7 facingthe cavity 12 are chemically treated or processed to make the portionsof the cover 6 and the spacer 7 facing the cavity 12 havehydrophilicity.

[0062] As specific methods for chemical surface treatment or processingon the portions of the cover 6 and the spacer 7 facing the cavity 12,there are, for example, corona discharge and glow discharge which aretypical plasma discharge processes. In such plasma discharge process, ahydrophilic functional group such as carboxyl group, hydroxyl group,carbonyl group or the like is formed on the surfaces of the cover 6 andthe spacer 7 facing the cavity 12, whereby the surface of the materialof the cover 6 and the spacer 7 is chemically reformed to increasesurface wettability.

[0063] Further, as materials of the cover 6 and the spacer 7 which canbe subjected to the above-mentioned chemical treatment, there arepolybutylene terephthalate, polyamide, polyvinyl chloride,polyvinylidene chloride, polyimide, nylon, and the like, in addition tothe above-mentioned polyethylene terephthalate and polycarbonate.

[0064] As described above, according to the third embodiment, thesurfaces of the cover 6 and the spacer 7 facing the cavity 12 into whichblood is drawn are subjected to the chemical treatment or processing forchemically reforming the surfaces, whereby the portions of the cover 6and the spacer 7 facing the cavity 12 have hydrophilicity. Therefore,wettability of the side walls of the cavity 12 is increased, whereby theblood sampled from the suction inlet 8 can be quickly and reliably drawninto the cavity 12. Accordingly, the surfactant layer 11 on the reagentlayer 10 is dispensed with, whereby the process of manufacturing thebiosensor can be simplified.

[0065] Further, as processes for chemically reforming the surfaceproperty, there are, besides plasma discharge, coupling reaction, ozonetreatment, ultraviolet treatment, and the like, and any of theseprocesses may be employed with the same effects as mentioned above.

[0066] Embodiment 4.

[0067] Hereinafter, a fourth embodiment of the present invention will bedescribed with reference to FIG. 1.

[0068] Initially, the construction of a biosensor according to thefourth embodiment will be described with reference to FIG. 1. In thefirst embodiment, a surfactant is mixed into the material itself of thecover 6 and the spacer 7 to make the portions of the cover 6 and thespacer 7 facing the cavity 12 have hydrophilicity. On the other hand, inthis fourth embodiment, the surfaces of the cover 6 and the spacer 7facing the cavity 12 are roughened to form fine and continuousrough-texture (asperities) on the material surface, thereby making theportions of the cover 6 and the spacer 7 facing the cavity 12 havehydrophilicity.

[0069] As specific methods for roughening the surfaces of the cover 6and the spacer 7, there are sand blasting, electric discharge, non-glaretreatment, mat treatment, chemical plating, and the like. The surfacesof the cover 6 and the spacer 7 facing the cavity 12 are roughened byany of these treatments to increase the surface wettability of the cover6 and the spacer 7.

[0070] Further, as materials of the cover 6 and the spacer 7 on whichsuch treatment can be performed, there are polybutylene terephthalate,polyamide, polyvinyl chloride, polyvinylidene chloride, polyimide,nylon, and the like, in addition to the above-mentioned polyethyleneterephthalate and polycarbonate.

[0071] As described above, according to the fourth embodiment, fine andcontinuous rough-texture (asperities) is formed on the surfaces of thecover 6 and the spacer 7 facing the cavity 12 to make the portions ofthe cover 6 and the spacer 7 facing the cavity 12 have hydrophilicity.Therefore, wettability of the side walls of the cavity 12 is increased,whereby the blood sampled from the suction inlet 8 can be quickly andreliably drawn into the cavity 12. Accordingly, the surfactant layer 11on the reagent layer 10 is dispensed with, whereby the process ofmanufacturing the biosensor is simplified.

[0072] Embodiment 5.

[0073] Hereinafter, a fifth embodiment of the present invention will bedescribed with reference to FIG. 1.

[0074] Initially, the construction of a biosensor according to the fifthembodiment will be described with reference to FIG. 1. In the first tofourth embodiments, the side walls of the cavity 12, i.e., the cover 6and the spacer 7 facing the cavity 12, are processed so as to havehydrophilicity. In this fifth embodiment, not only the cover 6 andspacer 7 but also the surface of the insulating support 5 on which theworking electrode 1, the counter electrode 2, and the reagent layer 10are formed, are subjected to any of the hydrophilic processes describedabove.

[0075] Hereinafter, a description will be given of the effects obtainedby subjecting, not only the cover 6 and the spacer 7, but also theinsulating support 5 to the hydrophilic process.

[0076] Initially, as a first effect, when the surface of the insulatingsupport 5 is processed so as to have hydrophilicity, suction of theliquid sample can be further promoted.

[0077] For example, in the case where the height of the suction inlet 8(≈ the thickness of the spacer 7) is relatively large (0.3 mm or more inthe sensor shown in FIG. 1), when the suction inlet 8 sucks, as a liquidsample, blood having a high hematocrit value under a low-temperatureenvironment (10° C. or lower), the effect of promoting the suction isnot satisfactorily obtained by making only the cover 6 and spacer 7 havehydrophilicity as described above, and the suction ability tends todecrease. So, as well as the cover 6 and the spacer 7, the insulatingsupport 5 is subjected the hydrophilic process as described for any ofthe first to fourth embodiments, whereby suction of the liquid samplecan be further promoted.

[0078] Next, as a second effect, when the electrodes are formed on thesurface of the insulating support 5 that has been processed so as tohave hydrophilicity, the adhesion of the electrodes to the insulatingsupport 5 is dramatically increased.

[0079] For example, in manufacturing biosensors, when a biosensor asshown in FIG. 1 is obtained by die-cutting an insulating support 5 witha press or the like according to the outline of the sensor afterbonding, onto the insulating support 5 on which plural electrodes andreagent layers 10 are formed, a spacer 7 having cut-out grooves forforming cavities 12 in positions corresponding to the respectiveelectrodes and reagent layers, and a cover 6 having air holes 9 in thecorresponding positions, the electrodes peel off from the insulatingsupport 5 or the electrodes are cracked due to a shock that occurs whenthe insulating support 5 is die-cut. This is because the electrodes areformed by printing a paste comprising a conductive material on theinsulating support 5 the polarity of which is inherently very small. So,the insulating support 5 is also subjected to the hydrophilic process asdescribed for any of the first to fourth embodiments to make thematerial surface of the insulating support 5, the surface of whichinherently has a very small polarity, have a polarity, whereby spreadand adhesion of the paste comprising a conductive material and used as amaterial of the electrodes are improved and, therefore, the electrodesare prevented from peeling off from the insulating support 5, or frombeing cracked.

[0080] As described above, according to the fifth embodiment, since notonly the cover 6 and the spacer 7 facing the cavity 12 but also theinsulating support 5 are subjected to the hydrophilic process, suctionof the blood sampled from the suction inlet 8 is further promoted ascompared with the case where only the cover 6 and the spacer 7 aresubjected to the hydrophilic process. Furthermore, since the insulatingsupport 5 is subjected to the hydrophilic process before formation ofthe electrodes to make the insulating support 5 have a polarity,adhesion of the electrodes to the insulating support 5 is increased,whereby peeling-off of the electrodes from the insulating support 5 andcracking of the electrodes, which have occurred during manufacturing ofthe sensor, are avoided. In the method of roughening the materialsurface, which is the hydrophilic process described for the fourthembodiment, the level of the rough surface (asperities) at which theeffect of adhesion can be expected is within a range of 0.001 μm˜1 μmand, especially, 0.01 μm˜0.1 μm are desirable.

[0081] Hereinafter, first and second examples of the present inventionwill be described.

EXAMPLE 1

[0082] On an insulating support 5 which comprises polyethyleneterephthalate and has been subjected to corona discharge (power: 400W,rate of discharge: 30 m/min), an electrode layer comprising a workingelectrode 1 and a counter electrode 2 is formed by screen printing, anda reagent layer 10 including an enzyme (glucose oxidase) and an electronacceptor (potassium ferricyanide) is formed on the electrode layer and,thereafter, a spacer 7 comprising polyethylene terephthalate is bondedto a cover 6 comprising polyethylene terephthalate in which about 1 % ofalkylbenzene sulfonate as an anionic surfactant is blended, therebyfabricating a blood sugar measuring sensor having a groove as acapillary tube into which blood is drawn.

[0083] Table 1 shows the blood suction ability of the sensor sofabricated. Here, a suction inlet 8 having a height of 0.15 mm and awidth of 2.0 mm is used. Each numeric value in Table 1 indicates a timerequired until the groove as a capillary tube into which blood is drawnis completely filled with the blood, under hostile environments(environmental temperature: 5° C., hematocrit: 65%), and the resultproves that the same blood suction promoting effect as that obtained bythe conventional senser is achieved. TABLE 1 conventional sensor sensorof Example 1 1 0.54 0.68 2 0.69 0.58 3 0.69 0.72 4 0.63 0.65 5 0.72 0.64average (sec) 0.65 0.65

[0084] While the indices of wettability (surface tension) of theinsulating support 5 and the cover 6 which comprise polyethyleneterephthalate used in Example 1 are 48 dyn/cm when they are notprocessed, the index of wettability at the surface of the insulatingsupport 5 after being subjected to corona discharge and that at thesurface of the cover 6 into which alkylbenzene sulfonate is blended are54 dyn/cm or more, and this result indicates that sufficient wettabilityfor promoting blood suction is secured.

[0085]FIG. 2 shows the result of a comparison of the sensorsensitivities at the blood glucose concentrations of 53˜992 mg/dl. Thesensor sensitivity is detected as follows. After the blood is drawn intothe capillary tube, a reaction between the reagent and glucose in theblood is promoted for about 25 seconds, and then a voltage of 0.5V isapplied between the leads 3 and 4. A current value detected five secondsafter the voltage application is the sensor sensitivity. Each numericalvalue in the graph shown in FIG. 2 is an average of n=10 times ofmeasuring. As shown in FIG. 2, the sensitivity of the sensor of Example1 is about 5% higher than the sensitivity of the conventional sensor.This attests to the result that the disuse of the surfactant layer 11increases the solubility of the reagent layer 10 that reacts with theblood.

[0086] Table 2 shows the result of a comparison of the repetitionaccuracy (CV values) in the 10-times measuring. It can be seen from theresult in Table 2 that the measuring variations in the sensor of Example1 (variations in each sensor) are significantly reduced as compared withthe measuring variations in the conventional sensor. TABLE 2 glucoseconcentration conventional sensor sensor of Example 1  53 mg/dl 6.25%3.79%  83 mg/dl 3.15% 1.67% 253 mg/dl 3.49% 1.53% 488 mg/dl 2.24% 0.60%596 mg/dl 2.49% 1.86% 992 mg/dl 2.23% 2.11%

[0087] As is evident from the results of FIG. 2 and table 2, ahighly-sensitive biosensor with less variations can be realized byemploying the sensor of Example 1.

[0088] Further, it is also confirmed how much the adhesion between theelectrode layer and the insulating support 5 is improved by subjectingthe surface of the insulating support 5 to corona discharge. A checkerpattern having 100 squares at 1 mm intervals is formed according toJISK5400 (general test method for coating; adhesion; checker-patterntaping method), and the degree of electrode peeling-off is checked withan adhesive cellophane tape. The result is as follows. While peeling-offof electrodes occurs at frequency of 5/100 squares in the conventionalsensor performing no corona discharge, it occurs at frequency of 0/100squares in the sensor of Example 1, that is, a clearly significantdifference is confirmed.

EXAMPLE 2

[0089] On an insulating support 5 comprising polyethylene terephthalate,an electrode layer comprising a working electrode 1 and a counterelectrode 2 is formed by screen printing, and a reagent layer 10including an enzyme (glucose oxidase) and an electron acceptor(potassium ferricyanide) is formed on the electrode layer and,thereafter, a spacer 7 comprising polyethylene terephthalate is bondedto a cover 6 comprising a compound film (the index of surfacewettability: 54 dyn/cm or more) which is obtained by laminating apolyester base resin having a hydrophilic polar group on polyethyleneterephthalate, thereby fabricating a blood sugar measuring sensor havinga groove as a capillary tube into which blood is drawn, and evaluationssimilar to those of Example 1 are executed. Table 3 shows the result ofa comparison of the blood suction rates between the sensor fabricated asdescribed above and the conventional sensor, FIG. 3 shows the result ofa comparison of the sensor sensitivities at the blood glucoseconcentrations of 53˜992 mg/dl, and Table 4 shows the result of acomparison of the repetition sensor accuracy (CV values) in 10-timesmeasuring. TABLE 3 conventional sensor sensor of Example 2 1 0.54 0.62 20.69 0.55 3 0.69 0.68 4 0.63 0.60 5 0.72 0.69 average (sec) 0.65 0.63

[0090] TABLE 4 glucose concentration conventional sensor sensor ofExample 2  53 mg/dl 6.25% 3.83%  83 mg/dl 3.15% 2.17% 253 mg/dl 3.49%1.22% 488 mg/dl 2.24% 1.60% 596 mg/dl 2.49% 1.56% 992 mg/dl 2.23% 2.05%

[0091] From these results, excellent blood suction ability and sensorresponsivity (sensitivity, CV value) as high as those of Example 1 areconfirmed.

[0092] Applicability in Industory

[0093] A biosensor according to the present invention is available as asensor which improves sensitivity and reduces variations when analyzinga specific component in a liquid sample which is drawn into a cavity ofthe sensor by capillary phenomenon.

1. A biosensor which is provided with a cavity into which a liquidsample is drawn by capillary phenomenon, and is able to analyze acomponent in the liquid sample by a reaction between the drawn liquidsample and a reagent, wherein the surface itself of at least a portionof side walls of the sensor, said side walls facing the cavity, hashydrophilicity.
 2. A biosensor as defined in claim 1 wherein the sidewalls of the sensor facing the cavity are made of a resin material inwhich a surfactant is mixed.
 3. A biosensor as defined in claim 2wherein the amount of the surfactant to be mixed is 0.01 weight % ormore.
 4. A biosensor as defined in claim 1 wherein the side walls of thesensor facing the cavity are made of a film the surface of which iscovered with a surfactant.
 5. A biosensor as defined in claim 1 whereinthe side walls of the sensor facing the cavity are made of a film thesurface of which is covered with a resin having a hydrophilic polargroup.
 6. A biosensor as defined in claim 4 or 5 wherein the thicknessof the surfactant or the resin having a hydrophilic polar group, whichcovers the film, is several tens of angstroms or more.
 7. A biosensor asdefined in claim 1 wherein the surface of at least a portion of the sidewalls forming the cavity is chemically reformed.
 8. A biosensor asdefined in claim 7 wherein a hydrophilic functional group is formed onthe surface of at least a portion of the side walls facing the cavity,by subjecting the surface to any of the following treatments: plasmadischarge, coupling reaction, ozone treatment, and UV treatment.
 9. Abiosensor as defined in claim 1 wherein the surface of at least aportion of the side walls facing the cavity is made of a rough surface.10. A biosensor as defined in claim 9 wherein a rough surface is formedat the surface of at least a portion of the side walls facing thecavity, by subjecting the surface to any of the following treatments:sand blasting, electric discharge, non-glare treatment, mat treatment,and chemical plating.
 11. A biosensor as defined in any of claims 1 to10 wherein the surface of the side wall, on which the reagent thatreacts with the liquid sample is formed, has hydrophilicity.
 12. Abiosensor as defined in any of claims 1 to 10 wherein the surface of theside wall, on which electrodes that detect the reaction between theliquid sample and the reagent are formed, has hydrophilicity.
 13. Abiosensor as defined in claim 12 wherein the surface of the support ismade of a rough surface, and the level of the rough surface to be formedis 0.001 μm to 1 μm.